title: Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats.
abstract: OBJECTIVE
  Many studies have demonstrated beneficial effects of either erythropoietin (EPO) or endothelial progenitor cell (EPC) treatment in cerebral ischemia. To improve post-ischemic tissue repair, we investigated the effect of systemic administration of endothelial colony-forming cells (ECFCs), considered as relevant endothelial progenitors due to their specific vasculogenic activity, in the presence or absence of EPO, on functional recovery, apoptosis, angiogenesis, and neurogenesis in a transient focal cerebral ischemia model in the adult rat.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  The rats were divided into four groups 24 hours after ischemia,, namely control, ECFCs, EPO, and ECFCs+EPO, and received a single intravenous injection of ECFCs (5 × 10(6) cells) and/or intraperitoneal administration of EPO (2500 UI/kg per day for 3 days).
  
  
  METHODS
  Infarct volume, functional recovery, apoptosis, angiogenesis, and neurogenesis were assessed at different time points after ischemia.
  
  
  RESULTS
  The combination of EPO and ECFCs was the only treatment that completely restored neurological function. The ECFCs+EPO treatment was also the most effective to decrease apoptosis and to increase angiogenesis and neurogenesis in the ischemic hemisphere compared to controls and to groups receiving ECFCs or EPO alone.
  
  
  CONCLUSIONS
  These results suggest that EPO could act in a synergistic way with ECFCs to potentiate their therapeutic benefits.
authors.affiliation: Aix Marseille Univ, INSERM UMR_S_1076, Marseille, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Youssef
authors.initials: Y
authors.lastname: Bennis
authors.forename: Benjamin
authors.initials: B
authors.lastname: Guillet
authors.forename: Lionel
authors.initials: L
authors.lastname: Velly
authors.forename: Philippe
authors.initials: P
authors.lastname: Garrigue
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bruder
authors.forename: Pascale
authors.initials: P
authors.lastname: Pisano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003131:Combined Modality Therapy; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin